Ali al-Asmari - Academia.edu (original) (raw)

Papers by Ali al-Asmari

Research paper thumbnail of E-learning in Saudi Arabia: Past, present and future

Near and Middle Eastern Journal of Research in Education, 2014

Research paper thumbnail of Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate

BMC Medical Genomics, 2016

Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelop... more Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelopmental disorders are thus heterogeneous. We applied whole exome sequencing (WES) for molecular diagnosis and in silico analysis to identify novel disease gene candidates in a cohort from Saudi Arabia with primarily Mendelian neurologic diseases. We performed WES in 31 mostly consanguineous Arab families and analyzed both single nucleotide and copy number variants (CNVs) from WES data. Interaction/expression network and pathway analyses, as well as paralog studies were utilized to investigate potential pathogenicity and disease association of novel candidate genes. Additional cases for candidate genes were identified through the clinical WES database at Baylor Miraca Genetics Laboratories and GeneMatcher. We found known pathogenic or novel variants in known disease genes with phenotypic expansion in 6 families, disease-associated CNVs in 2 families, and 12 novel disease gene candidates in 11 families, including KIF5B, GRM7, FOXP4, MLLT1, and KDM2B. Overall, a potential molecular diagnosis was provided by variants in known disease genes in 17 families (54.8 %) and by novel candidate disease genes in an additional 11 families, making the potential molecular diagnostic rate ~90 %. Molecular diagnostic rate from WES is improved by exome-predicted CNVs. Novel candidate disease gene discovery is facilitated by paralog studies and through the use of informatics tools and available databases to identify additional evidence for pathogenicity. Not applicable.

Research paper thumbnail of Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy

American journal of human genetics, Jan 3, 2016

The paradigm of a single gene associated with one specific phenotype and mode of inheritance has ... more The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been impl...

Research paper thumbnail of ADAT3 -related intellectual disability: Further delineation of the phenotype

American Journal of Medical Genetics Part A, 2016

ADAT3-related intellectual disability has been recently described in 24 individuals from eight Sa... more ADAT3-related intellectual disability has been recently described in 24 individuals from eight Saudi families who had cognitive impairment and strabismus. Other common features included growth failure, microcephaly, tone abnormalities, epilepsy, and nonspecific brain abnormalities. A single homozygous founder mutation (c.382G>A:p.(V128M)) in the ADAT3 gene, which encodes a protein that functions in tRNA editing, was identified in all affected individuals. In this report, we present additional 15 individuals from 11 families (10 Saudis and 1 Emirati) who are homozygous for the same founder mutation. In addition to the universal findings of intellectual disability and strabismus, the majority exhibited microcephaly and growth failure. Additional features not reported in the original cohort include dysmorphic facial features (prominent forehead, up-slanted palpebral fissures, epicanthus, and depressed nasal bridge), behavioral problems (hyperactivity and aggressiveness), recurrent otitis media, and growth hormone deficiency. ADAT3-related intellectual disability is an important recognizable cause of intellectual disability in Arabia. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Nonketotic hyperglycinemia in Suleimaniah Children's Hospital, Riyadh, Saudi Arabia

Research paper thumbnail of Goldenhar syndrome and hereditary tyrosinemia type 1

Saudi medical journal, 2002

We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1), to our knowledge... more We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1), to our knowledge an association not previously described. This case further increases the diversity of observations and clinical descriptions of patients with this complex syndrome. We discuss pathogenetic aspects, and demonstrate further evidence of the effectiveness of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione in the treatment of HTT1.

Research paper thumbnail of Prescribing patterns for acute respiratory infections in primary health care, aseer region, saudi arabia

Journal of family & community medicine, 2005

The objective of this study was to identify the patterns of prescribing for Acute respiratory inf... more The objective of this study was to identify the patterns of prescribing for Acute respiratory infections in patients attending primary health care centers in the Aseer region, southwestern Saudi Arabia. MATERIALS #ENTITYSTARTX00026; This study was conducted at primary health care centers in the Aseer region during November 2003. A master sheet designed by the investigator was distributed to all the working physicians in the primary health care center in the Aseer region. The master sheet included the age, sex, complaints, signs, clinical diagnosis and the type of medications prescribed. Physicians were asked to include all patients attending on 17(th) November 2003, and send the master sheet to the Technical Supervision Unit at Primary Care Department, General Directorate of Health Affairs. Data of the master sheet was entered and analyzed by using SPSS. The total number of patients attending with acute respiratory infections(ARIs) was 3000 which represented 25% of the patients atte...

Research paper thumbnail of Mutations in FBXL4 Cause Mitochondrial Encephalopathy and a Disorder of Mitochondrial DNA Maintenance

The American Journal of Human Genetics, 2013

Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetica... more Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in three unrelated consanguineous kindreds in which affected children present with a fatal encephalopathy, lactic acidosis, and severe mtDNA depletion in muscle. We show that FBXL4 is an F-box protein that colocalizes with mitochondria and that loss-of-function and splice mutations in this protein result in a severe respiratory chain deficiency, loss of mitochondrial membrane potential, and a disturbance of the dynamic mitochondrial network and nucleoid distribution in fibroblasts from affected individuals. Expression of the wild-type FBXL4 transcript in cell lines from two subjects fully rescued the levels of mtDNA copy number, leading to a correction of the mitochondrial biochemical deficit. Together our data demonstrate that mutations in FBXL4 are disease causing and establish FBXL4 as a mitochondrial protein with a possible role in maintaining mtDNA integrity and stability.

Research paper thumbnail of Atypical presentations of propionic acidemia

Health, 2012

One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) whi... more One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched chain Amino Acids and other metabolites. Classically this disease presented with high anion gap metabolic acidosis with its clinical consequences. We report 4 patients who presented to our facility with sepsis like picture and no metabolic acidosis. All of them were found to have high ammonia level. Diagnosis was confirmed by tandem MS/MS and urine Gas Chromatography/ Mass Spectrometry (GC/MS). All of them were treated supportively and by supplementation of adequate calories and PA formula. The different presentations may be very well attributed to the PCC molecular defects heterogeneity. Mutations in both genes PCCA and PCCB can cause PA with more frequent heterogeneity of PCCA gene. In spite of the fact that PCCB gene is responsible for the most of the oriental cases, our first patient condition was attributed to PCCA gene with a rare mutation which was not described in the literatures.

Research paper thumbnail of E-learning in Saudi Arabia: Past, present and future

Near and Middle Eastern Journal of Research in Education, 2014

Research paper thumbnail of Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate

BMC Medical Genomics, 2016

Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelop... more Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelopmental disorders are thus heterogeneous. We applied whole exome sequencing (WES) for molecular diagnosis and in silico analysis to identify novel disease gene candidates in a cohort from Saudi Arabia with primarily Mendelian neurologic diseases. We performed WES in 31 mostly consanguineous Arab families and analyzed both single nucleotide and copy number variants (CNVs) from WES data. Interaction/expression network and pathway analyses, as well as paralog studies were utilized to investigate potential pathogenicity and disease association of novel candidate genes. Additional cases for candidate genes were identified through the clinical WES database at Baylor Miraca Genetics Laboratories and GeneMatcher. We found known pathogenic or novel variants in known disease genes with phenotypic expansion in 6 families, disease-associated CNVs in 2 families, and 12 novel disease gene candidates in 11 families, including KIF5B, GRM7, FOXP4, MLLT1, and KDM2B. Overall, a potential molecular diagnosis was provided by variants in known disease genes in 17 families (54.8 %) and by novel candidate disease genes in an additional 11 families, making the potential molecular diagnostic rate ~90 %. Molecular diagnostic rate from WES is improved by exome-predicted CNVs. Novel candidate disease gene discovery is facilitated by paralog studies and through the use of informatics tools and available databases to identify additional evidence for pathogenicity. Not applicable.

Research paper thumbnail of Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy

American journal of human genetics, Jan 3, 2016

The paradigm of a single gene associated with one specific phenotype and mode of inheritance has ... more The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been impl...

Research paper thumbnail of ADAT3 -related intellectual disability: Further delineation of the phenotype

American Journal of Medical Genetics Part A, 2016

ADAT3-related intellectual disability has been recently described in 24 individuals from eight Sa... more ADAT3-related intellectual disability has been recently described in 24 individuals from eight Saudi families who had cognitive impairment and strabismus. Other common features included growth failure, microcephaly, tone abnormalities, epilepsy, and nonspecific brain abnormalities. A single homozygous founder mutation (c.382G>A:p.(V128M)) in the ADAT3 gene, which encodes a protein that functions in tRNA editing, was identified in all affected individuals. In this report, we present additional 15 individuals from 11 families (10 Saudis and 1 Emirati) who are homozygous for the same founder mutation. In addition to the universal findings of intellectual disability and strabismus, the majority exhibited microcephaly and growth failure. Additional features not reported in the original cohort include dysmorphic facial features (prominent forehead, up-slanted palpebral fissures, epicanthus, and depressed nasal bridge), behavioral problems (hyperactivity and aggressiveness), recurrent otitis media, and growth hormone deficiency. ADAT3-related intellectual disability is an important recognizable cause of intellectual disability in Arabia. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Nonketotic hyperglycinemia in Suleimaniah Children's Hospital, Riyadh, Saudi Arabia

Research paper thumbnail of Goldenhar syndrome and hereditary tyrosinemia type 1

Saudi medical journal, 2002

We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1), to our knowledge... more We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1), to our knowledge an association not previously described. This case further increases the diversity of observations and clinical descriptions of patients with this complex syndrome. We discuss pathogenetic aspects, and demonstrate further evidence of the effectiveness of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione in the treatment of HTT1.

Research paper thumbnail of Prescribing patterns for acute respiratory infections in primary health care, aseer region, saudi arabia

Journal of family & community medicine, 2005

The objective of this study was to identify the patterns of prescribing for Acute respiratory inf... more The objective of this study was to identify the patterns of prescribing for Acute respiratory infections in patients attending primary health care centers in the Aseer region, southwestern Saudi Arabia. MATERIALS #ENTITYSTARTX00026; This study was conducted at primary health care centers in the Aseer region during November 2003. A master sheet designed by the investigator was distributed to all the working physicians in the primary health care center in the Aseer region. The master sheet included the age, sex, complaints, signs, clinical diagnosis and the type of medications prescribed. Physicians were asked to include all patients attending on 17(th) November 2003, and send the master sheet to the Technical Supervision Unit at Primary Care Department, General Directorate of Health Affairs. Data of the master sheet was entered and analyzed by using SPSS. The total number of patients attending with acute respiratory infections(ARIs) was 3000 which represented 25% of the patients atte...

Research paper thumbnail of Mutations in FBXL4 Cause Mitochondrial Encephalopathy and a Disorder of Mitochondrial DNA Maintenance

The American Journal of Human Genetics, 2013

Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetica... more Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in three unrelated consanguineous kindreds in which affected children present with a fatal encephalopathy, lactic acidosis, and severe mtDNA depletion in muscle. We show that FBXL4 is an F-box protein that colocalizes with mitochondria and that loss-of-function and splice mutations in this protein result in a severe respiratory chain deficiency, loss of mitochondrial membrane potential, and a disturbance of the dynamic mitochondrial network and nucleoid distribution in fibroblasts from affected individuals. Expression of the wild-type FBXL4 transcript in cell lines from two subjects fully rescued the levels of mtDNA copy number, leading to a correction of the mitochondrial biochemical deficit. Together our data demonstrate that mutations in FBXL4 are disease causing and establish FBXL4 as a mitochondrial protein with a possible role in maintaining mtDNA integrity and stability.

Research paper thumbnail of Atypical presentations of propionic acidemia

Health, 2012

One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) whi... more One of the most common recessively inherited organic acidemias is the Propionic Acidosis (PA) which results from Propionyle-CoA Carboxylase (PCC) enzyme deficiency that is necessary for the catabolism of the branched chain Amino Acids and other metabolites. Classically this disease presented with high anion gap metabolic acidosis with its clinical consequences. We report 4 patients who presented to our facility with sepsis like picture and no metabolic acidosis. All of them were found to have high ammonia level. Diagnosis was confirmed by tandem MS/MS and urine Gas Chromatography/ Mass Spectrometry (GC/MS). All of them were treated supportively and by supplementation of adequate calories and PA formula. The different presentations may be very well attributed to the PCC molecular defects heterogeneity. Mutations in both genes PCCA and PCCB can cause PA with more frequent heterogeneity of PCCA gene. In spite of the fact that PCCB gene is responsible for the most of the oriental cases, our first patient condition was attributed to PCCA gene with a rare mutation which was not described in the literatures.